Severe acute respiratory syndrome (“SARS”) is highly communicable human disease. In the spring of 2003, a sudden, unexpected world-wide epidemic occurred in which more than 8000 people were believed to have been infected and more than 800 are known to have died (see Pearson et al., Nature 424:121 (2003)). Although the 2003 epidemic was stemmed by infection control measures, the infection could re-emerge at any time and has the potential to cause a global pandemic as devastating as HIV/AIDS (De Groot, Vaccine 21:4095-104 (2003)).
The etiologic agent of SARS was rapidly identified as a new coronavirus (SARS-CoV) (see Rota et al, Science 300:1394-99 (2003)); Marra et al., Science 300:1399 (2003)) and found to cause a similar respiratory disease in a non-human primate model (see Fouchier et al., Nature 423:240 (2003); Kuiken et al., Lancet 362:263-70 (2003)). SARS is a highly communicable illness consisting of fever and respiratory symptoms that can progress to pneumonia, respiratory failure, and death. Infrequently, a subclinical or non-pneumonic form of the syndrome may also exist (see Ho et al., J. Infect Dis. 189:634-41 (2004); Woo et al., Lancet 363:841-45 (2004)).
Effective prophylaxis and therapies are urgently needed in the event that there is reemergence of the highly contagious and often lethal severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) infection. Currently, prevention of SARS has largely relied on improved awareness, surveillance, and institution of local, regional and international public-health-care measures (see Stadler et al., Nat Rev Microbiol 1:209-18 (2003)). Significant efforts in the area of SARS vaccine research have been initiated and several recent reports have documented that transfer of immune serum from mice with prior SARS-CoV infection, or from mice vaccinated with a DNA plasmid encoding SARS S protein or a vaccinia virus expressing the S protein, can prevent virus replication in the lungs and upper respiratory tract (see Bisht et al., Proc. Natl. Acad Sci USA 101:6641-46 (2004); Subbarao et al., J Virol 78:3572-77 (2004); Yang et al., Nature 428:561-64 (2004)). In addition, in SARS-CoV infection of humans, decreasing virus titers from nasopharyngeal aspirates, serum, urine and stool have been observed to be coincident with the development of neutralizing antibodies (see Li et al., N Engl Med 349:508-09 (2003); Peiris et al., Lancet 361:1767-72 (2003)). Treatment of SARS with convalescent plasma has been reported (see Burnouf et al., Hong Kong Med. J. 9:309-10 (2003); Wong et al., Hong Kong Med. J. 9:199-201 (2003)).
These studies support the importance of humoral immunity in protection against SARS-CoV and suggest that a specific and effective human monoclonal antibody (MAb) should be developed to provide a prophylaxis and early treatment against SARS in the event that episodic or even widespread reemergence into the human population occurs.